Penn Medicine scientists Katalin Kariko and Drew Weissman have been awarded the 2023 Nobel Prize in Physiology or Medicine for discoveries enabling the development of mRNA vaccines.
| Photo Credit: Peggy Peterson/Penn Medicine, Reuters

The 2023 Nobel Prize for physiology or medicine has been awarded to the Hungarian biochemist Katalin Karikó and the American physician-scientist Drew Weissman. According to the Royal Swedish Academy of Science,  they have been feted for “discoveries concerning nucleoside base modification that enabled the development of effective mRNA vaccines against COVID-19”.

Dr. Karikó is only the thirteenth woman to win the prize.

That the citation mentions the pandemic is testament to the effect mRNA vaccines had on its evolution as well as how the global disaster became an opportunity for these vaccines’ technology to showcase its potential.

mRNA stands for messenger RNA, a type of molecule that carries instructions from the DNA to a cell’s cytoplasm, where those messages are ‘read’ to produce various proteins. In the late 1980s, scientists realised that mRNA could become the basis for a new kind of vaccines if some hurdles could be overcome.

The idea was to inject the body with a modified mRNA that would instruct cells to build a certain protein, which could then provoke the body’s immune system to ‘attack’ it as well as prepare itself to encounters with the same protein in future. This protein could be something produced by a virus – such as the spike protein of SARS-CoV-2. But the mRNA would have to survive its journey inside the body and be able to enter a cell.

Dr. Karikó and Dr. Weissman began to collaborate in the late 1990s. They and other scientists published many studies until 2004 elucidating the steps from delivering mRNA into a body (such as of a rat) to the immune system responding. But one problem remained. The immune system sensed the synthetic mRNA to be a foreign substance that needed to be eliminated but not the cells’ mRNA. Why?

A study the duo published in 2005, with Michael Buckstein and Houping Ni, had the answer: the cells’ mRNA underwent chemical reactions that modified it in certain ways, whereas the synthetic mRNA remained unchanged.

RNA is made up of smaller molecules called bases. Dr. Karikó and Dr. Weissman reported that when they modified some of these bases in the synthetic mRNA and delivered it to cells, the cells produced more provocative proteins than they did without the modifications. They had found out how foreign mRNA could enter a body and then its cells without setting off alarm bells.

They published two more studies that set the stage for the use of an mRNA platform for a new kind of vaccine. In 2020, the COVID-19 pandemic dawned on the world, and mRNA vaccines played a pivotal role – if also one overtaken by the dubious virtues of vaccine nationalism – in lowering its death toll.

“You can start a production cycle in the morning and by evening have enough for tests,” former Indian Institute of Science, Bengaluru, director Govindarajan Padmanabhan told The Hindu in October 2022 about the advantage of mRNA vaccines. Currently, scientists are exploring their use against influenza, dengue, and some cancers and auto-immune diseases.

Dr. Drew Weissman arrives for the Ninth Breakthrough Prize Ceremony at the Academy Museum of Motion Pictures in Los Angeles, California, U.S., April 15, 2023.
| Photo Credit: Reuters

Drew Weissman’s decades of research into mRNA technology paved the way for Covid-19 vaccines, finally earning a Nobel prize for the physician-scientist.

The 64-year-old University of Pennsylvania immunologist, who won the Nobel Medicine Prize along with long-time collaborator Katalin Kariko on Monday, is far from done.

His next quests include, among others, developing a vaccine against all future coronaviruses.

“There have been three (coronavirus) pandemics or epidemics in the past 20 years,” Weissman told AFP recently, referring to the original SARS virus, MERS and Covid-19.

“You have to assume there’s going to be more, and our idea was that we could wait for the next coronavirus epidemic or pandemic, and then spend a year and a half making a vaccine. Or we could make one now.”

Twin breakthroughs

The world is now aware of the elegance of the mRNA (messenger ribonucleic acid) vaccines, that deliver genetic instructions to cells telling them to recreate the spike protein of the coronavirus, in order to trigger effective antibodies when they encounter the real thing.

But back when Weissman teamed up with Kariko in the 1990s, the research was considered a scientific dead-end, and working with DNA was considered a more promising avenue.

“We started working together in 1998, and that was without much funding and without much in the way of publications,” he said.

In 2005, the pair found a way to alter synthetic RNA to stop it from causing a massive inflammatory response found in animal experiments.

“Just before our paper was published, I said ‘Our phones are going to ring off the hook,'” he recalls.

“We sat there staring at our phones for five years, and they never rang!”

With a second big breakthrough in 2015, they found a new way to deliver the particles safely and effectively to their target cells, using a fatty coating called “lipid nanoparticles.”

Both developments are part of the Pfizer and Moderna Covid-19 vaccines today.

Helping people

Weissman grew up in Lexington, Massachusetts.

His father and mother, both since retired, were an engineer and dental hygienist, respectively.

“When I was five years old, I was diagnosed as a type-one diabetic, and back then it was testing urine and taking insulin shots a few times a day,” he recalled, and this motivated him to pursue science.

He was educated at Brandeis University and completed an MD-Phd program in immunology at Boston University.

As a young fellow at the National Institutes of Health, he worked for several years in Anthony Fauci’s lab on HIV research, before finally arriving at his long-time home Penn.

Weissman was a practicing doctor until a few years ago, and says it brings him great joy that his invention has helped save millions of lives.

“I’m a clinician scientist, my dream since starting college and medical school was to make something that helps people. I think I can say that I’ve done that. So I am incredibly happy,” he said.

Beyond vaccines, mRNA technology is also being heralded for its potential across medicine.

Weissman’s team is working on using RNA to develop a single-injection gene therapy to overcome the defect that causes sickle cell anemia, a genetic blood disease that 200,000 babies are born with in Africa every year.

Significant technical challenges remain to ensure the treatment is able to correctly edit genes and is safe, but the researchers are hopeful.

Bone marrow transplant, an expensive treatment with serious risks, is currently the only cure.

Hungarian biochemist Katalin Kariko poses for a photo in Budapest, Hungary, May 27, 2021. Two scientists have won the Nobel Prize in medicine on Monday, Oct. 2, 2023 for discoveries that enabled the development of mRNA vaccines against COVID-19. The award was given to Katalin Karikó and Drew Weissman. Karikó is a professor at Sagan’s University in Hungary and an adjunct professor at the University of Pennsylvania.
| Photo Credit: AP

Hungarian-born scientist Katalin Kariko’s obsession with researching a substance called mRNA to fight disease once cost her a faculty position at a prestigious US university, which dismissed the idea as a dead end.

Now, her pioneering work — which paved the way for the Pfizer/BioNTech and Moderna Covid-19 vaccines — has won her the Nobel Prize in Medicine.

Kariko, 68, spent much of the 1990s writing grant applications to fund her research into “messenger ribonucleic acid” — genetic molecules that tell cells what proteins to make, essential to keeping our bodies alive and healthy.

She believed mRNA held the key to treating diseases where having more of the right kind of protein can help — like repairing the brain after a stroke.

But the University of Pennsylvania, where Kariko was on track for a professorship, decided to pull the plug after the grant rejections piled up.

Also Read | India-made mRNA vaccine priced at ₹2,292, will be available as a booster dose

“I was up for promotion, and then they just demoted me and expected that I would walk out the door,” she told AFP in an interview from her home in Philadelphia in December 2020.

Kariko didn’t yet have a green card and needed a job to renew her visa. She also knew she wouldn’t be able to put her daughter through college without the hefty staff discount.

She decided to persist as a lower-rung researcher, scraping by on a meagre salary.

It was a low point in her life and career, but “I just thought…you know, the (lab) bench is here, I just have to do better experiments,” she said.

The determination runs in the family — her daughter Susan Francia did go to UPenn, where she earned a master’s degree, and won gold medals with the US Olympic rowing team in 2008 and 2012.

Twin breakthroughs

By the late 1980s, much of the scientific community was focused on using DNA to deliver gene therapy, but Kariko believed that mRNA was also promising since most diseases are not hereditary and don’t need solutions that permanently alter our genetics.

First though, she had to overcome a major problem: in animal experiments, synthetic mRNA was causing a massive inflammatory response as the immune system sensed an invader and rushed to fight it.

Explained | Who is manufacturing India’s mRNA vaccine?  

Kariko, together with her main collaborator and co-winner Drew Weissman, discovered that one of the four building blocks of the synthetic mRNA was at fault — and they could overcome the problem by swapping it out with a modified version.

They published a paper on the breakthrough in 2005. Then, in 2015, they found a new way to deliver mRNA into mice, using a fatty coating called “lipid nanoparticles” that prevent the mRNA from degrading, and help place it inside the right part of cells.

Both these innovations were key to the Covid-19 vaccines developed by Pfizer and its German partner BioNTech, where Kariko is now a senior vice president, as well as the shots produced by Moderna.

Both work by giving human cells the instructions to make a surface protein of the coronavirus, which simulates an infection and trains the immune system for when it encounters the real virus.

Explained | How can mRNA vaccines help fight cancer? 

New treatments

Though she does not want to make too much of it, as a foreign-born woman in a male-dominated field, Kariko occasionally felt underestimated — saying people would approach after lectures and ask “Who’s your supervisor?”

“They were always thinking, ‘That woman with the accent, there must be somebody behind her who is smarter or something,'” she said.

Yet the Nobel is just the latest accolade for Kariko, who has won the Breakthrough Prize, the L’Oreal-UNESCO prize for women in science awards, among many others.

It is a far cry from the time when her late mother would call every year after prize announcements to ask why she hadn’t been chosen.

“I never in my life get (federal) grants, I am nobody, not even faculty,” she would reply with a laugh.

To which her mother would reply: “But you work so hard!”

The Nobel Prizes for 2023 in Medicine or Physiology has been awarded to Katalin Karikó and Drew Weissman

This year’s Nobel Prize for Physiology or Medicine has been jointly awarded to Katalin Karikó and Drew Weissman for their “discoveries concerning nucleoside base modification that enabled the development of effective mRNA vaccines against COVID-19”, The Royal Swedish Academy of Science announced on October 2, 2023.

Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times, the press release said.

Last year the Nobel Prize for Physiology was awarded to Swedish scientist Svante Pääbo “for his discoveries concerning the genomes of extinct hominins and human evolution.” Dr. Pääbo’s pioneering work in an entirely new discipline—paleogenomics—has helped the scientific community understand human evolution and migration at a deeper level.

Thanks to his groundbreaking research, we now have a genome sequence of our closest hominin relatives—the Neanderthals. Dr. Pääbo and his group has also analysed several additional genome sequence from extinct hominins.

The Prize for Physiology or Medicine kicks off a week of Nobel Prize announcements. The winners for Physics will be announced on October 3, followed by Chemistry on October 4. The winners of the Literature, Peace and Economic Sciences Prize will be declared on October 5, October 6 and October 9 respectively.

The prizes carry a cash award of 10 million Swedish kronor (nearly $900,000) and will be awarded on December 10. The money comes from a bequest left by the prize’s creator, Swedish inventor Alfred Nobel, who died in 1895.